2310 ch 16.pptx

Chapter 16 Acquired specific immunity is a product of B and T lymphocytes. • Lymphocytes undergo a selective process that specializes them for reacting to only one specific antigen/immunogen. • Immunocompetence is the ability of the body to react with countless foreign substances. Characteristic...

Chapter 16 Acquired specific immunity is a product of B and T lymphocytes. • Lymphocytes undergo a selective process that specializes them for reacting to only one specific antigen/immunogen. • Immunocompetence is the ability of the body to react with countless foreign substances. Characteristics of the Specific Immunity Highly specific to the antigen against which the third line of defense is directed. You can react to any antigen you encounter. Turned on by second-line cells. After activation, mitosis produces many clones. Prevents autoimmune diseases. The rapid mobilization of lymphocytes that have been programmed to recall their first engagement with the invader. Lymphocyte Development and Differentiation Antigen Presentation Second-line phagocyte is called an antigen presenting cell (APC). Lymphocyte Response Major Stages in the Development of B and T cells Each naïve lymphocyte bears an antigen receptor that recognizes a unique antigen. Lymphocytes that formed in the bone marrow become either B or T cells. • B cells stay in the bone marrow. • T cells migrate to the thymus. • Each builds a unique antigen receptor. • Both B and T cells migrate to secondary lymphoid tissues. • By the time B and T cells reach the lymphoid tissues, each one is equipped to respond to a single, unique antigen. B cells mature in the bone marrow. • Hundreds of millions of distinct B cells develop as a result of gene modification and selection. • Circulate through the blood, “homing” to specific sites in the lymph nodes, spleen, and other lymphoid tissue where they take up residence. The specific B-cell receptor is called an immunoglobulin. • An immunoglobulin is an antibody. • Constant region made up of “heavy” protein chain at its base. • Variable region made up of “light” protein chains that bind to antigens. • B-cells release same free-floating antibodies that bind to the antigen and disarm it. • Y-shaped arrangement has two binding sites. Mechanism Behind Antibody Variability • Antigen-binding sites are highly variable in shape to fit a wide range of antigens. • The gene for the binding region has many interchangeable sections. • During maturation of the B-cell some segments randomly combine and others are deleted. T Cell Receptors Similar to the B cell receptor: • Formed by genetic modification. • Also has variable and constant regions. • Inserted into the membrane. • Has antigen binding site formed from two parallel polypeptide chains. Unlike the immunoglobulins: • Relatively small. • Never secreted. T cell versus B cell receptors • B cell receptors recognize many types of molecules. • T cell receptors recognize only proteins. Clonal deletion removes any potentially harmful clones. • Known as central tolerance. • Basis of immune tolerance or tolerance to self. • Lymphocytes at the periphery of the body have mechanisms for not reacting to innocuous agents. • Some autoimmune diseases are thought to be caused by the loss of immune tolerance, the survival of “forbidden clones,” or failure of other systems. Antigen Challenge and Clonal Selection B cells and T cells proliferate and differentiate when challenged by antigen. Clone: • Proliferation of a particular lymphocyte. • Genetically identical cells, some of which are memory cells. Clonal Selection Theory of Lymphocyte Development and Diversity Antigens are chemical substances that bind to immune cells. • Protein or polysaccharide molecules on or inside cells and viruses. • Antigens that stimulate a response by immune cells are immunogens. • Many antigens are not considered immunogens because they don’t cause an immune response (ex. our own body made compounds, household cleaners, foods). Characteristics of Antigens Must be perceived as foreign: • Whole microbes or their parts. • Cells or substances that arise from other humans, animals, plants, and various molecules. • Molecules of complex composition such as proteins or protein-containing compounds are more immunogenic than repetitious polymers composed of a single unit. A substance must be large enough to catch the attention of surveillance cells to initiate an immune response. • Generally, large antigens are better than small antigens at getting an immune response. • Antigens are too small by themselves to elicit an immune response are haptens. • If haptens are linked to a carrier group (i.e. another molecule), the combined molecule develops immunogenicity. Hapten-Carrier Phenomenon Epitopes are the portion of the antigen molecule recognized and responded to by a lymphocyte. • The primary signal that a molecule is foreign. • A single antigen (ex. surface a virus) may have many different epitopes. • Each epitope reacts with a different subtype of B and T cell. • So a virus may trigger dozens of different antibodies and cytotoxic T cells! Alloantigens are cell surface markers that occur in some members of the same species but not in others. • Proteins and other molecules of one person that are antigenic to another. • Ex. different blood types A, B, O • Responsible for rejections of organ and tissue transplants. Superantigens are potent stimuli for T cells. • Activate T cells at a rate 100 times greater than ordinary antigens. • Can result in an overwhelming release of cytokines and cell death. • Is coronavirus a superantigen in some people?? Seems so! Major Histocompatibility Complex (MHC) is a set of closely linked polymorphic genes that code for cell surface proteins. • Class I genes code for markers that appear on all nucleated cells and platelets. They present antigens from within the cell. • MHC I markers themselves act as antigens in transplants. • Class II genes code for markers on antigen presenting cells (APCs) such as macrophages, dendritic cells, and B cells. • MHC II markers present antigens to T cells. Classes I and II of Molecules of the Human Major Histocompatibility Complex MHC Display • MHC I displays endogenous protein fragments. • Normal cells display normal protein fragments. • Infected host cells and malignant host cells display foreign/abnormal protein fragments. • MHC II displays exogenous protein fragments. Cluster of differentiation (CD) molecules are used to identify different immune cells. • Have different functions such as assisting with antigen recognition and docking or initiating a signal cascade within the cell. • Close to 400 have been described. • T helper (TH) cells are CD4 cells which binds to MHC class II molecules. • Cytotoxic (TC) cells are CD8 cells which binds MHC class I molecules. Surfaces of T Cells and B Cells Presentation of Antigens APCs present antigens in the following steps. 1. Ingest the pathogens and induce an inflammatory response in the tissue if appropriate. 2. Process and present antigen to T-lymphocytes. • Some migrate to the nearest lymphoid organ. Other present to lymphocytes in the tissue. Antigen presenting cells: • Dendritic cells • Macrophages • B cells Antigens must be further acted upon and formally presented by antigen-presenting cells (APCs). Dendritic Cell Engulfing a Fungal Spore T Cell Overview CD4 Cell Activation Cell-Mediated Immunities • Require the direct involvement of T lymphocytes throughout the course of the reaction. • Among the most complex and diverse in the immune system. • Involve several subsets of T cells whose actions are dictated by the APCs that activate them. • T cells require some type of MHC recognition before they can be activated. • All produce cytokines with a spectrum of biological effects. A stimulated naive T helper cell differentiates into different T helper types. • Helper T cells (TH): activate macrophages, assist B-cell processes, strengthen inflammatory response, and help activate cytotoxic T cells. • Regulatory T cells (TR): control the T-cell response. • Control the inflammatory process. • Prevent autoimmunity. • Make sure the immune response does not inappropriately target normal biota. • Memory T cells: quickly convert into large numbers of effector T cells upon re-exposure to the specific invading antigen. CD8 Cell Activation Cytotoxic T (Tc) Cells: Cells That Kill Other Cells. Cytotoxicity: • The capacity of certain T cells to kill a specific target cell. Killer T cell (CD8) activation: • Must recognize a foreign peptide complexed with self MHC-I presented to it and mount a direct attack on a target cell. Target cells: • Virally infected cells • Cancer cells • Cells from other animals and humans Cytotoxic T Cell Secretions After Activation Perforins: • Proteins that punch holes in the membranes of target cells. • Causes ions to leak out of target cells. • Creates a passageway for granzymes to enter. Granzymes: • Enzymes that attack proteins of target cells. After attack with perforins and granzymes, the targeted cells go through death by apoptosis. B cell Overview When activated by antigen, a B cell divides, giving rise to plasma cells. • Each plasma cell has the same reactive profile. • Release antibodies into the tissue and blood. • Attach to the antigen for which they are specific and mark it for destruction or neutralization. Events in B-cell Activation Events in B-cell Differentiation and Antibody Synthesis Basic Immunoglobulin (Ig) Molecule • Four polypeptide chains connected by disulfide bonds. • Two functionally distinct fragments: • Antigen-binding fragments (Fab): 2 variable regions. • Constant fragment (Fc): 1 region. Antibody Functions Classes of Immunoglobulins IgG - Monomer IgA - Dimer, Monomer IgM - Pentamer IgD Monomer IgE - Monomer Number of antigen binding sites 2 4, 2 10 2 2 Molecular weight 150,000 170,000-385,000 900,000 180,000 200,000 Percentage of total antibody in serum 80% 13% 6% 1% 0.002% Average half-life in serum (days) 23 6 5 3 2.5 Crosses placenta? Yes No No No No Fixes complement? Yes No Yes No No Fc binds to Phagocytes Biological function Long-term immunity; memory antibodies; neutralizes toxins, opsonizes, fixes complement Mast cells and basophils Secretory antibody; on mucous membranes Produced at first response to antigen; can serve as B-cell receptor Receptor on B cells Antibody of allergy; worm infections IgE stimulates mast cells to recruit eosinophils. IgA is present in secretions from mucous membranes. Monitoring Antibody Production Over Time Titer: • The concentration of antibodies in the serum. • Can be measured over time to determine how the immune system reacts to antigen. Primary Response • Occurs with the first exposure to antigen. • Latent period: • Marked by a lack of antibody production. • Antigen is concentrated in lymphoid tissues. • As plasma cells produce antibodies, serum titer increases to a plateau, and then tapers off to a low level over weeks and months. Secondary Response or Amnesiatic Response • Occurs when the immune system is exposed again to the same immunogen weeks, months, or even years later. • Rate of antibody synthesis, peak titer, and length of antibody response is greatly increased over the primary response. • The idea behind vaccination…when you are exposed to the real viable pathogen you have a secondary response instead of the immune response. Primary and Secondary Responses to Antigens